INTRODUCTION:Deficiency or impaired activity of alpha-1-antitrypsin (AAT), which neutralizes multiple proteolytic enzymes, such as collagenases and elastases may result in significant tissue autodigestion. Hence, AAT may have a role in the healing process in chronic and acute inflammation including skin infection, such as cellulitis.AIM:The aim of this study was to evaluate the role of AAT activity and inflammatory markers in patients with cellulitis.METHODS:The study included eleven consecutive patients (6 males and 5 females, mean age 68.5 ± 4.5 years) who were hospitalized for cellulitis between 09/2009-02/2010. We analyzed tests results for C reactive protein (CRP), AAT level and activity that were obtained on admission (T1), 2 days after admission (T2) and 2 weeks after admission (T3).RESULTS:AAT levels were found to be within the normal range. AAT activity values were found to be within or above the normal range. The highest activity values were measured after 2 days of treatment and the lowest values were measured after 2 weeks of treatment. CRP values were highest on admission and lowest, as expected, after the end of treatment 2 weeks later. AAT activity values were significantly lower statistically in patients with unresolved cellulitis 2 weeks after treatment began.SUMMARY:AAT activity was significantly lower statistically in patients who suffered from slow resolving cellulitis 14 days after hospitalization. This possibly suggests a role AAT activity may have in the inflammation cascade in patients with cellulitis. Further studies are needed to evaluate the role of AAT activity in the inflammatory process.

BACKGROUND:Physical restraints are a common, albeit controversial, tool used in the acute care setting.OBJECTIVES:To determine the prevalence of physical restraint use in an acute care hospital. Secondary objectives were to determine whether physical restraints are used more commonly in night shifts, identify patient risk factors for physical restraint use, and establish if staff-to-patient ratio correlated with physical restraint use.METHODS:An observational cross-sectional study was conducted over 3 months in 2013 in the medical, surgical and intensive care units in a mid-sized general hospital. All the physically restrained patients in each observation were added to the registry. At each observation one department was selected for comparison and all non-restrained patients were added to the registry.RESULTS:The study population comprised 2163 patients. Seventy-six were restrained and 205 were included as case-controls. The prevalence of physical restraint use was 3.51% (95% CI = 2.79-4.37%). Physical restraint use was more common in night shifts than day shifts: 4.40% vs. 2.56% (P = 0.03). Male gender, dependency, invasive ventilation, invasive tubes (nasogastric tube or urine catheter), and bedsores were all significantly correlated with restraint use. Staff-to-patient ratios were not significantly correlated with use of physical restraints.CONCLUSIONS:Physical restraints are relatively common in acute care wards. The use of physical restraints seems to correlate with certain patient characteristics but not with staff-to-patient ratios, and seems more common at night.

Gout is rare among young women. The prevalence of gout is increasing in the western world and the Far East, probably owing to life style changes. The association between hyperuricemia and gout, the metabolic syndrome and atherosclerosis is stronger in women. 40 years ago, the increased prevalence of hyperuricemia and gout in Filipino men living in the United States was described. Recently, Filipino men and women living in the western world were found to have increased risk of the metabolic syndrome and atherosclerosis. We describe two unusual cases of gout in premenopausal Filipino women living in Israel, both of which suffered from hypertension. We also describe the current knowledge about gout in women, in general, and in migrant Asian women, in particular, with an emphasis on its relations to the metabolic syndrome and atherosclerosis. The occurrence of gout in relatively young migrant Filipino women might signal a change in the epidemiology of this disease, and might signal that these women are more prone to develop the metabolic syndrome and its complications.

Among the key effects of fluid shear stress on vascular endothelial cells is modulation of gene expression. Promoter sequences termed shear stress response elements (SSREs) mediate the responsiveness of endothelial genes to shear stress. While previous studies showed that shear stress responsiveness is mediated by a single SSRE, these endogenous promoters often encode for multiple SSREs. Moreover, hybrid promoters encoding a single SSRE rarely respond to shear stress at the same magnitude as the endogenous promoter. Thus, to better understand the interplay between the various SSREs, and between SSREs and endothelial-specific sequences (ESS), we generated a series of constructs regulated by SSREs cassettes alone, or in combination with ESS, and tested their response to shear stress and endothelial specific expression. Among these constructs, the most responsive promoter (NR1/2) encoded a combination of two GAGACC/SSREs, the Sp1/Egr1 sequence, as well as a TPA response element (TRE). This construct was four- to five-fold more responsive to shear stress than a promoter encoding a single SSRE. The expression of constructs containing other SSRE combinations was unaffected or suppressed by shear stress. Addition of ESS derived from the Tie2 promoter, either 5′ or 3′ to NR1/2 resulted in shear stress transcriptional suppression, yet retained endothelial specific expression. Thus, the combination and localization order of the various SSREs in a single promoter is crucial in determining the pattern and degree of shear stress responsiveness. These shear stress responsive cassettes may prove beneficial in our attempt to time the expression of an endothelial transgene in the vasculature.

Background: Mixed hyperlipidemia is a common disorder characterized by elevated VLDL and LDL levels. Patients with this syndrome usually are in need of combination therapy, comprising a fibric acid derivate with a statin drug in order to achieve LDL and triglyceride target values. Atorvastatin is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor demonstrated to be effective in reducing both cholesterol (CHOL) and triglyceride (TG) levels in humans. We examined the efficacy of atorvastatin as monotherapy in achieving a better or the same lipid profile in patients with mixed hyperlipidemia treated with combination therapy.Design: We compared atorvastatin with a combination of a fibric acid derivate and a statin drug (other than atorvastatin) in a 24-week, prospective randomized, open-label study of 27 patients with mixed hyperlipidemia.Methods: All 27 patients had been treated with statin-fibrate therapy in different regimens for at least a year. Atorvastatin at a daily dose of 20 mg was substituted for statin-fibrate therapy. Lipid and safety profiles were assessed.Results: Atorvastatin significantly reduced total cholesterol, LDL-C, and HDL-C compared to statin-fibrate therapy. In contrast, TG and glucose levels were significantly elevated with atorvastatin. Target LDL-C and TG was achieved in 10 patients with the single therapy of atorvastatin vs. 6 patients under statin-fibrate. In 16 patients, atorvastatin was at least as effective as, or better than, the combination therapy, and was recommended for continuation of treatment.Conclusion: Atorvastatin is an adequate monotherapy for many mixed hyperlipidemia patients. We recommend atorvastatin be considered for every patient suffering from mixed hyperlipidemia. (C) 2007 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Obesity is an independent risk factor for ischemic heart disease and affects the status of other risk factors for cardiovascular disease.OBJECTIVE:To study the attitude of physicians to obesity by examining discharge letters of overweight patients with ischemic heart disease.METHODS:We used the HOLEM database for this analysis. The HOLEM project was designed to study the NCEP (National Cholesterol Education Program) guideline implementation among patients with IHD at hospital discharge. We documented the recording of risk factors and treatment recommendations for IHD by reviewing the discharge letters of 2994 IHD patients admitted to four central hospitals in Israel between 1998 and 2000. A follow-up visit was held 6-8 weeks after discharge, at which time the diagnosis of IHD was verified, risk factor status was checked, height and weight were measured and drug treatment was reviewed.RESULTS:Mean body mass index was 28.3 kg/m2 and 32% were obese (BMI > or = 30 kg/m2). Only 39.6% of the obese patients and 65.8% of the morbidly obese patients (BMI > or = 40 kg/m2) had "obesity" noted in their discharge letters, and weight loss recommendation was written in only 15% of the obese patients' discharge letters. Acute episodes like acute myocardial infarction and unstable angina did not influence the notation of obesity, and only BMI and the number of additional risk factors were positively correlated with the notation of this risk factor.CONCLUSIONS:Despite the importance of obesity, weight status was not noted and weight loss was not recommended in most of the discharge letters of obese IHD patients.

Only a limited number of cases of Behçet's disease and hematological malignancies have been reported in the literature. We report the case of a 45 year old female patient with Behçet's disease who developed myelodysplastic syndrome, refractory anemia with excess blasts in transformation subtype, with complex chromosomal abnormalities, including excess of chromosome 8, following several years of treatment with chlorambucil for Behçet's disease. As has been described in most such cases, gastrointestinal involvement was most prominent. This case is described and the occurrence of myelodysplastic syndrome in Behçet's disease reviewed.

BACKGROUND:Hypercholesterolemia control status is lacking throughout the western world.OBJECTIVES:To examine whether the treatment recommendations given to ischemic heart disease patients at hospital discharge are compatible with the guidelines of the Israeli medical societies and the U.S. National Cholesterol Education Program for coronary artery disease prevention; and to study the effects of brief educational sessions on the adherence of physicians with the guidelines.METHODS:We included consecutive IHD patients admitted to four central hospitals in Israel between 1998 and 2000. The study was conducted in two phases. In phase 1, we reviewed discharge letters to document treatment recommendations given to each patient. In phase 2 we educated the practitioners by reviewing the Israeli medical societies and the NCEP guidelines and the quality of their recommendations in phase 1, after which we reevaluated the discharge letters.RESULTS:The study included 2,994 patients: 627 in phase 1 and 2,367 in phase 2. Of the patients who needed cholesterol-lowering according to their low density lipoprotein levels, 37.4% were not prescribed such drugs at discharge (under-treatment group). This proportion was reduced by education to 26.6% (P < 0.001) in phase 2. Of the treated patients, 65.6% did not reach the target LDLgoal in phase 1 (under-dosage group) as compared to 60.2% in phase 2 (P = 0.23). In phase 2 there was an increase in the percent of patients reaching LDL levels <130 mg/day (69.3% vs. 63.8% of patients prescribed medication, P = 0.01), but the percent of patients reaching' LDL levels <100 was not different in phase 2 after adjusting for age and gender (the odds ratio for reaching target LDL was 1.16, with 95% confidence interval of 0.95-1.43).CONCLUSIONS:Physician recommendations to IHD patients discharged from hospital were suboptimal. We documented a high proportion of under-treated and under-dosaged patients. Brief educational sessions have a beneficial effect on the usage of statins; however, additional effort in guideline implementations is needed.

Statins (HMG-CoA reductase inhibitors) are the most commonly used lipid lowering drugs. Recent experimental evidence suggest that these agents appear to display additional cholesterol independent or pleiotropic effects, contributing to prevention and inhibition of atherosclerosis. In addition, clinical trials have demonstrated different effects of statins on diseases that are not directly related to accelerated atherosclerosis. The statins' vascular pleiotropic effects include improvement of endothelial function, slowing the inflammation process, inhibition of the thrombus formation, enhancement of plaque stability and decreasing oxidative stress. Clinical benefits were observed with statins therapy for cardiovascular diseases - ischemic heart disease, cerebral vascular accidents and peripheral vascular disease. Lately, clinical trials have suggested their role in Alzheimer's disease, multiple sclerosis, malignant diseases, osteoporosis, chronic renal diseases, transplantations, macular degeneration and autoimmune diseases. The objective of this review is to summarize the data related to the pleiotropic effects of the statin drugs, beyond their lipid lowering effect.

We report a case of a young woman with pyrexia and progressive lung disease who developed acute respiratory distress syndrome (ARDS) and required prolonged mechanical ventilator support. The patient had a markedly elevated serum ferritin concentration of 7880 mug/L, a specific finding for the adult onset Still's disease (AOSD). Treatment of the patient with supportive and immunosuppressive therapy, resulted in patient survival and cure. The early consideration of the diagnosis of AOSD in patients with fever of unknown origin and a compatible clinical course may modify its severe complications.

Blood-flow interactions with the vascular endothelium represents a specialized example of mechanical regulation of cell function that has important physiological and pathophysiological cardiovascular consequences. Yet, the mechanisms of mechanostransduction are not understood fully. This study shows that shear stress induces a rapid induction as well as nuclear translocation of the vascular endothelial growth factor (VEGF) receptor 2 and promotes the binding of the VEGF receptor 2 and the adherens junction molecules, VE-cadherin and β-catenin, to the endothelial cytoskeleton. These changes are accompanied by the formation of a complex containing the VEGF receptor 2–VE-cadherin–β-catenin. In endothelial cells lacking VE-cadherin, shear stress did not augment nuclear translocation of the VEGF receptor 2 and phosphorylation of Akt1 and P38 as well as transcriptional induction of a reporter gene regulated by a shear stress-responsive promoter. These results suggest that VEGF receptor 2 and the adherens junction act as shear-stress cotransducers, mediating the transduction of shear-stress signals into vascular endothelial cells.

Coronary artery disease is a polygenic disease whose phenotypic manifestation depends on the interaction of the genetic background with a number of environmental factors. Recently, the gene coding for the angiotensin-converting enzyme (ACE) has been characterized and a deletion/insertion (D/I) polymorphism was defined. The prevalence of the three genotypes and their association with coronary artery disease (CAD) differ in different population groups. Mostly, the D allele was found as a significant risk factor for CAD, independently from other risk factors. In the present study, we determined the distribution of ACE alleles (D or I) in a cohort of healthy Israeli men and examined the correlation of the different genotypes with various CAD risk factors. We found LDL cholesterol levels to be highest in the DD genotype group, intermediate in the DI genotype group and lowest in the II genotype group. We also found higher blood pressure levels in subjects bearing the D allele compared to II homozygous subjects. In conclusion, it appears that the genetic influence of the D/I polymorphism on CAD manifests primarily through traditional risk factors.

Some cancer patients demonstrate low levels of plasma cholesterol. This has been explained as resulting from a defect in the cholesterol feedback control in tumor cells. The objective of this study was to determine the presence of a relationship between cholesterol metabolism and regulation, and between the occurrence of mutated Ras protein activity. Total cholesterol mass in Ras-mutated rat embryo fibroblasts was 2 times less than that in control cells (non-mutated fibroblasts). Low-density lipoprotein (LDL) uptake, as determined by 125I-labeled LDL degradation was 2-fold higher in the Ras-mutated cells. Downregulation of LDL uptake in both mutated and non-mutated cells was similar. Cholesterol synthesis in the mutated cells was lower by 50–66%, compared with non-mutated cells. There was no change in cholesterol efflux between the two cell lines. Thus, it appears that in these mutated cells, overutilization of the farnesyl pathway results in decreased accumulation of cholesterol in the cells. We suggest that a relationship between mutated Ras protein activity and cholesterol metabolism is present.

Since its introduction in 1985, the new fluoroquinolone antibiotic ofloxacin has gained widespread use, and much information has accumulated about its possible adverse effects. Skin reactions have been uncommon, and there have been very few reports about hypersensitivity vasculitis directly related to ofloxacin. The authors report such a case, in which the patient needed plastic surgery because of severe vasculitis in both legs.

Background: Increasing evidence suggests that oxidized low-density lipoprotein (LDL) is associated with the development of atherosclerosis in vivo. Because endothelial injury contributes to the development of the atherogenic plaque, we investigated the effect of oxidized LDL on the integrity of human umbilical cord endothelial cells (HUVECs) by analyzing cytotoxicity and cell detachment. Methods: The cellular integrity of cultured endothelial cells was evaluated using cytotoxicity and detachment assays of cells labeled with chromium-51. Results: Low concentrations of oxidized LDL (25–50 μg protein/ml) induced morphological changes (cell elongation and formation of gaps in the cobblestone monolayer), decreased cellular cytotoxicity (by 13% compared with control), and also decreased cell detachment (by 22% compared with control). At higher concentrations of oxidized LDL (100 μg protein/ml), however, increases in cytotoxicity (by up to 70%) and cellular detachment (by up to 90%) were demonstrated. Native LDL, which was not oxidized in our cell system, did not induce any changes either in cytotoxicity or in cell detachment. The protective effect of low oxidized LDL concentrations against endothelial cell cytotoxicity and detachment was abolished by indomethacin (2μM), indicating the involvement of prostaglandin synthesis in this protection. Conclusion: Our experiments suggest that oxidized LDL-induced alterations of endothelial cells involve a sequence of events leading from a non-cytotoxic protective stage to endothelial perturbation.

Hypocholesterolemia has been reported in patients with disseminated cancer. In this study we evaluated the effect of tumor cells on two processes that lead to enhanced clearance from plasma of low density lipoprotein (LDL), the main carrier of cholesterol: (1) LDL uptake by non-tumor cells; (2) LDL oxidative modification. Incubation of control normal cells (bovine smooth muscle cells or human skin fibroblasts) with conditioned medium (CM) from ras mutated fibroblasts (RAS+) resulted in a 49 and 31% increase in the cellular LDL uptake, respectively, in comparison to cells incubated with CM from non-mutated fibroblasts (RAS−). Serum samples derived from patients with disseminated cancer also promoted cellular uptake of LDL by J-774 A.1 macrophages by up to twofold. Cellular mediated oxidative modification of LDL, measured as TBARS formation, was significantly higher when LDL was incubated with RAS+, or with MCF-7 tumor cells under oxidative stress, in comparison to LDL incubated with non-tumor cells. Furthermore, LDL incubated with MCF-7 tumor cells had undergone physicochemical modifications, as evaluated by a decrease in the lipoprotein fluidity by 26%, when compared to the fluidity of LDL that was incubated with J-774 A.1 cells. In conclusion the results indicate that tumor cells induce accelerated LDL uptake by non-tumor cells and stimulate LDL oxidative modification. Both processes may result in hypocholesterolemia.

The most common etiology of atrial mass, a rare disorder, is thrombosis. However, tumors, vegetations and fibrosis may also be responsible. Today, 2-dimensional echocardiography is the primary imaging technique for screening patients with a suspected cardiac mass. We describe a 66-year-old woman with chronic atrial fibrillation who was being treated with an anticoagulant for a year. A left atrial thrombus, which produced signs simulating those of mitral stenosis became dislodged and obstructed the abdominal aorta and superior mesenteric artery. She did not survive operation.

A patient with anemia and elevated erythrocyte sedimentation rate presented with sudden hearing loss. The diagnosis of temporal arteritis was verified by temporal biopsy. Initiation of corticosteroid therapy reversed the disease manifestations and within a short period improved the patient's hearing.